Background: Heart failure (HF) prognosis without therapy is poor, however introduction of a range of drugs has improved it. We aimed to perform a protocol for systematic review and meta-analysis on the effects and safety of Sodium-Glucose Transporter 2 inhibitors in HF patients. Methods: This protocol of systematic review and meta-analysis has been drafted under the guidance of the preferred reporting items for systematic reviews and meta-analyses protocols. This study will use the PubMed, Cochrane Library, Embase, Web of Science, and Medline databases. In addition, we will also collect 4 databases of China: China National Knowledge Infrastructure, China Biomedical Literature Database, China Science Journal Database, and Wan-fang Database. The risk of bias of included studies is estimated by taking into consideration the characteristics including random sequence generation, allocation concealment, blinding of patients, blinding of outcome assessment, completeness of outcome data, selective reporting and other bias by Cochrane Collaboration's tool. All analyses were performed with Review Manager (RevMan) software, version 5.3 (Update Software Ltd, Oxford, Oxon, UK). Results: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. Conclusion: Sodium-glucose transporter 2 inhibitors may improve critical outcomes in HF patients, and it is apparently safe.